CN116635201A

CN116635201A - Method and system for producing microstructures

Info

Publication number: CN116635201A
Application number: CN202280008400.XA
Authority: CN
Inventors: 迈克尔·库里克; 奥尔加·格鲁恩瓦尔德; 菲利普·鲁斯; 尼哥拉依·蒂辛
Original assignee: LTS Lohmann Therapie Systeme AG
Current assignee: LTS Lohmann Therapie Systeme AG
Priority date: 2021-01-12
Filing date: 2022-01-12
Publication date: 2023-08-22
Also published as: JP2024505414A; EP4277776A1; DE102021100396A1; WO2022152734A1; US20240058995A1; CA3200921A1

Abstract

The invention relates to a method for producing a microstructure (120), comprising the following steps: providing a planar mold element (10) comprising at least one mold opening (12) for a microstructure (120) to be produced, wherein the at least one mold opening (12) has a first opening (14) and a second opening (18); providing a first agent (22) at the second opening (18); generating a negative pressure in the mould opening (12); and absorbing the first agent (22) into the mold opening (12) through the second opening (18) due to the negative pressure in the mold opening (12). The invention also relates to a system (100) for producing microstructures.

Description

Method and system for producing microstructures

Technical Field

The present invention relates to a method for producing microstructures, and in particular to a method for producing microarrays. The invention also relates to a system for producing microstructures, in particular to a system for producing microarrays.

Background

Microarrays have a plurality of microneedles, which are typically disposed in, or attached to, a support element such as a patch, a drug film, or the like. The length of the microneedles is specifically sized such that when the microneedles are pushed into the skin of a patient, the microneedles penetrate the skin only to the extent that the tips of the needles do not contact the nerves and blood vessels, and the needles include an active ingredient, such as a drug, if possible. The corresponding active ingredient may be provided on the upper side of the needle or in the needle. When the active ingredient is disposed in the needle, the needle or a component of the needle is made of a material that dissolves in the skin of the patient.

Microarrays are produced using, for example, a silicone mold having a plurality of mold openings. To fill the mold opening, a liquid with an active ingredient is typically applied to the upper side of the silicone mold. After the liquid has dried, another liquid is applied, if necessary. The support element is applied to the underside of the material introduced into the silicone mold, and the microneedles are removed from the silicone mold and then encapsulated.

Currently, the production of microarrays is very complex and expensive.

Moreover, problems arise when filling generally conical or pyramidal mold openings. The filling material often does not adequately fill the mold opening. For example, cavities and/or air inclusions may occur. This problem arises in particular in the tips of conical or pyramidal mould openings. Such defective filling may lead to problems, for example during application, because, for example, a defective tip cannot penetrate the skin properly and/or an under-dosing of the active ingredient may occur due to loss of the formulation from the cavity.

Contamination and/or staining causes additional problems in current microarray production.

Disclosure of Invention

The object of the present invention is to provide a method for producing microstructures, in particular microarrays, wherein scalability (scalability) is improved and the method is preferably suitable for mass production. It is a further object of the present invention to provide a corresponding system for producing microstructures.

According to the invention, this object is achieved by a method according to claim 1 and a system according to claim 18.

The present method for producing microstructures is in particular a method for producing microarrays. The preferred first step of the method comprises providing a preferably two-dimensional mold element. The mold element has at least one, preferably a plurality of mold openings for the microstructures to be produced. In particular, at least one of the mould openings is a negative mould for the microstructure to be produced. The mold opening corresponds in particular to the cavity. The at least one mould opening comprises a first opening and a second opening, in particular positioned opposite the first opening. Thus, it is preferred that the mould opening is open on both sides. Preferably, the first opening and the second opening open the mold opening to the environment. Preferably, the first opening and the second opening form a fluid connection between the mould opening and the environment. The mould opening preferably extends from one side of the two-dimensional mould element to the side of the mould element opposite to the first side. In a preferred embodiment, if the mould element is designed as a membrane, the mould opening extends in particular from one side of the membrane to the other side of the membrane. Preferably, the at least one mold opening is an imprint mold opening, preferably made using an imprint roller. Additional steps of the method include providing a first formulation at the second opening. Preferably, the first formulation comprises at least one active ingredient. The first formulation is specifically designed to form a microstructured tip. In particular, the provision of the first formulation brings the formulation into contact with the second opening. It is particularly preferred that the second opening is provided so as to be immersed in the first formulation. Another step of the method includes generating negative pressure and/or suction in the mold opening. The negative pressure may also be referred to as vacuum, preferably not complete vacuum. Here, the negative pressure means, in particular, a negative pressure ratio with respect to the ambient pressure. A further, in particular next step of the method comprises the step of sucking the first formulation into the mould opening through the second opening. The suction is at least partially achieved by the negative pressure in the mold opening. In this respect, it is preferred that the first formulation is inhaled through the second opening. In addition to the absorption of the first formulation due to the negative pressure, it is preferred that the first formulation is absorbed into the mould opening due to capillary action. Preferably, such absorption by capillary action occurs before and/or during absorption by negative pressure. The uptake of the first formulation into the mould opening is in particular performed to form part of the microstructure to be produced. In particular, the suction is aspiration or suction.

In a preferred embodiment, the negative pressure is generated in the mould opening by expanding the volume of the mould opening. In particular, the volume to be expanded is the volume between the first opening and the second opening of the mould opening. Preferably, the expansion of the volume of the opening of the mould is effected such that the resulting volume expansion corresponds approximately to the volume of the first formulation to be absorbed. In particular, the volume expansion of the mould opening is at least 3%, preferably at least 5%, particularly preferably at least 10%, more preferably at least 20%.

Preferably, a further step of the method comprises reducing the volume of the mould opening, wherein this step is performed before generating the negative pressure in the mould opening, in particular before expanding the volume of the mould opening. The step of providing the first formulation is preferably performed before and/or after the volume reduction. Preferably, a reduction in the volume of the opening of the mould is achieved such that the resulting volume reduction corresponds approximately to the volume of the first formulation to be absorbed. In particular, the volume of the mould opening is reduced by at least 3%, preferably by at least 5%, particularly preferably by at least 10%, more preferably by at least 20%.

Preferably, the volume of the mould opening is reduced by at least partially compressing the mould element. Compression here means in particular compression and/or longitudinal expansion. For compression, it is preferred that the mould element is pressed on one side of the first opening, preferably on both sides of the two openings, and/or that the mould element expands, in particular in the longitudinal direction.

Preferably, the compression mold element is performed using at least one roller. In particular, the roller is a press roller. At least one pressure roller presses against at least one surface of the mould element, in particular the surface of the first opening of the mould element. It is particularly preferred that the compression is performed on both sides of the mould element using two rollers. Preferably, the two rollers are arranged offset in the rolling direction.

Further steps of the method preferably comprise arranging an auxiliary element on the side of the mould element having the first opening. The auxiliary element is connected to the contact, in particular to it, preferably by means of an adhesive. The auxiliary element preferably comprises an auxiliary film and in particular consists thereof. The placement of the auxiliary element is preferably performed before the generation of the negative pressure in the mould opening, particularly preferably before the volume expansion of the mould opening. In particular, the auxiliary element is arranged before or during the reduction of the volume of the mould opening.

Preferably, the further step of the method comprises closing the first opening of the mould opening. In particular, the first opening is closed in a substantially airtight manner. Preferably, the closing is performed using an auxiliary element, such that the auxiliary element seals the first opening of the mould opening. The step of closing the first opening is performed before a negative pressure is generated in the mould opening. In particular, closing the first opening is performed after a reduction of the volume of the mould opening, preferably after compression of the mould element.

A preferred further step of the method comprises preferably removing the auxiliary element from the mould element. This removal is performed after the first formulation is absorbed into the mold opening. Preferably, the removal is performed by means of a peeling auxiliary element.

Preferably, the shape of the at least one die opening is cylindrical or conical. The cylindrical or conical shape has in particular a circular, triangular or quadrangular cross section, with a square cross section being particularly preferred. Preferably, the conical shape tapers from the first opening to the second opening. It is possible that the conical shape is designed as a truncated cone. Conical shapes with angular cross sections can also be described as pyramids.

The second opening preferably comprises a smaller cross-sectional area than the first opening. The cross-section of the mould shape preferably tapers from the first opening towards the second opening.

The reduction of the volume of the mould opening, in particular the at least partial compression of the mould element, is preferably performed by bending the mould element. The bending is effected in particular in the transverse direction of the mould element, so that in particular one bending edge is perpendicular to the longitudinal direction of the mould element. It is particularly preferred to perform the bending in the direction of the first opening and/or in the direction opposite to the tapering direction of the mould opening, in particular in the case of a conical mould opening. Thus, preferably, the compression portion (strand) of the mould element is located on one side of the first opening and/or on the side on which the mould opening is enlarged. The bending is performed in particular at an angle of between 0 ° and 180 °, preferably between 10 ° and 90 °, particularly preferably between 30 ° and 60 °. Due to the bending, the mold element has in particular a neutral portion and a compressed portion on the side of the mold element where the bending is performed and an expanded portion on the side opposite to the compressed portion. Thus, preferably, there is a compression portion on one side of the compression portion of the mold element and a tension portion on one side of the expansion portion of the mold element. The bending preferably has the effect that the compression section, in particular the compression section, of the mould element becomes smaller. In particular, the volume of the mold opening, preferably of the mold opening, is thereby also reduced in this region of the mold element. Likewise, the bending thereby preferably enlarges the stretched portion, in particular the unfolded portion, of the mould element. In particular, the volume of the mold opening, preferably of the mold opening, is thereby also increased in this region of the mold element. In a preferred embodiment, in particular in an embodiment with a conically shaped mould opening, the mould opening has a larger volume, in particular a significantly larger volume, on the side of the compression part than on the side of the expansion part. Thus, the bending preferably reduces the volume on the side of the compression portion more than the volume on the side of the expansion portion. In general, it is preferred that the reduction in the total volume of the die opening is caused by bending.

The bending is preferably performed using at least one roller. At least one of the rollers is preferably a curved roller.

The expansion of the volume is performed in particular by restoring the mould element to in particular the original shape. It is particularly preferred that the recovery is a re-bending of the curved mould element by a bending operation and/or a relaxation of the compressed, in particular extruded and/or longitudinally expanded mould element.

Preferably, the mould element comprises, in particular consists of, a membrane.

It is particularly preferred that the mold element comprises, in particular consists of, TPU, PC or PETG.

The mould element is preferably compressible. Preferably, the mould element is elastic.

Preferably, after the step of absorbing the first formulation, the second formulation is provided at the first opening. Preferably, the second formulation is free of active ingredients. However, it is also possible that the second formulation comprises at least one active ingredient. After the second formulation is provided, the second formulation is received through the first opening into the mold opening. Preferably, in doing so, the mold opening, in particular the remaining volume of the mold opening, is completely filled with the second formulation. In particular, the second agent is bound to the first agent, in particular by substance-to-substance binding. Preferably, the second formulation is absorbed by pushing in, in particular pressing in. Pushing is preferably performed using rollers. Preferably, in the step of taking up, the formulation is contacted with the first opening on one side and covered by a formulation element, in particular a second formulation element described below, on the other side. Preferably, a pressure for pushing in the second formulation, in particular a roller, is applied to the formulation element.

Preferably, the first formulation is provided using a first formulation element. The first formulation element preferably comprises, in particular consists of, a membrane. The first formulation element includes a first formulation. Preferably, the first formulation is arranged on the first formulation element, in particular in the form of droplets. Preferably, the first formulation element comprises a formulation receiving portion, which preferably comprises a recess. In other words, the formulation receiving part is a type of bowl-shaped mould in the formulation element in which the formulation is located. Alternatively or in addition to providing the first formulation by means of a first formulation element, a second formulation element comprising a second formulation is used to provide the second formulation. In particular, the second formulation element is similarly implemented with one or more features of the first formulation element.

Drying is performed in particular after the first formulation has been absorbed and/or the second formulation has been absorbed. Drying the first formulation and/or the second formulation is particularly performed via the first opening of the mould opening. The drying is carried out in particular by means of a preferably warm air stream which is in particular in direct contact with the first and/or second formulation. Preferably, the drying cures the first formulation and/or the second formulation to form a microstructure. In addition to or as an alternative to the air flow, drying may be achieved using thermal radiation, in particular infrared radiation.

A preferred further step of the method comprises metering the first formulation and/or the second formulation. The test is performed in particular by means of an optical test device. Preferably, the optical test device comprises a camera. The test is performed after the first formulation and/or the second formulation is absorbed. It is particularly preferred that the test is performed after or before the drying step.

Preferably, the first formulation, which has been at least partially cured to form a microstructure, and the second formulation, which is preferably combined with the first formulation, are demolded. Demolding is performed at and through the first opening of the mold opening. Preferably, the demolding is carried out after drying, particularly preferably after testing. Preferably, demolding is performed at the second formulation.

Preferably, the demolding is performed using a cover element. In particular, the cover element comprises, in particular consists of, a cover film. The cover member is coupled to either the first agent or the second agent. Preferably, the attachment is a substance-to-substance bond, in particular an adhesive bond. Alternatively or in addition to demolding by means of the cover element, demolding is performed by removing, in particular by stripping, the mold element. Preferably, the cover element is a second formulation element, such that demolding is performed using the second cover element.

Preferably, the released microstructure is packaged. Preferably, the packaging is performed using blister elements. Packaging with a blister film is particularly preferred.

The method is performed in particular with a system having one or more of the features of the system described below.

The present system for producing microstructures is particularly a system for producing microarrays. In particular, the system is a device. The system is specifically designed to implement the above method. It is particularly preferred that the system comprises one or more of the above-mentioned features, in particular the device features described therein. The system includes a mold element. The mould element is in particular compressible or elastic. The mould element comprises at least one mould opening for the microstructure to be produced. In particular, at least one of the mould openings is a negative mould for the microstructure to be produced. The mold opening corresponds in particular to the cavity. The mould opening preferably comprises a first opening and in particular a second opening located opposite the first opening. The mould opening is open in particular on both sides, so that the mould element comprises at least one continuous mould opening. Preferably, the first opening and the second opening open the mold opening to the environment. Preferably, the first opening and the second opening form a fluid connection between the mould opening and the environment. Further, the system comprises a compression device. The compression device is in particular a compression and/or bending device. The compression device preferably comprises, and in particular consists of, a roller, particularly preferably a compression roller and/or a bending roller. The compression device is configured to compress the mold element. In particular, the compression means are arranged and/or configured to act in an extruded manner on the mould element and/or to bend the mould element. In a preferred embodiment, the compression means is configured to reduce the volume of the mould opening by compression.

Preferably, the compression device has two opposing rollers, in particular a compression roller and/or a bending roller. In particular, the rollers are arranged such that the mold elements can be compressed, in particular pressed and/or bent, between the rollers. The mould element is preferably arranged between the rolls. In particular, the rollers are arranged offset relative to each other in the roller guiding direction.

Preferably, the system comprises a preferably sterile isolator, wherein at least the compression device and at least a portion of the mold element are arranged.

The mould element of the method according to the invention and/or of the system according to the invention is in particular a mould element according to DE 10 2020 125 484A1.

Drawings

The invention is described in more detail below with the aid of preferred embodiments with reference to the accompanying drawings.

In the accompanying drawings:

fig. 1a to 1d are schematic cross-sectional side views showing a production state of the method according to the invention, wherein fig. 1b also shows an embodiment of a system for producing microstructures according to the invention;

fig. 2a to 2c are schematic cross-sectional side views showing a production state of the method according to the invention, wherein fig. 2c also shows an embodiment of a system for producing microstructures according to the invention;

fig. 3 is a schematic cross-sectional side view showing the production state of the method according to the invention, while also showing an embodiment of the system for producing microstructures according to the invention;

FIG. 4 is a schematic cross-sectional side view showing a production state of an embodiment of the method according to the invention; and

fig. 5 is a schematic cross-sectional side view showing an embodiment of the method according to the invention and showing a production state of another embodiment of the system for producing microstructures according to the invention.

In the drawings, similar or identical parts or elements are identified with the same reference numerals or variants thereof (12, 12' and 12 "). In particular, for the sake of clarity, it is preferred that the elements already identified are not provided with reference numerals in all figures.

Detailed Description

Fig. 1a shows a mould element 10, which in this case is designed in particular as a film 11. At the illustrated upper surface, the membrane 11 has a first side 16 and an opposite second side 20. A conical or pyramidal die opening 12 extends through the membrane 11. On the first side 16, the mold opening 12 has a first opening 14. The die opening 12 tapers from the first side 16 to the second side 20, wherein the second opening 18 is formed on the second side 20. On the second side 20, a first formulation 22, preferably comprising an active ingredient, is arranged in contact with the second opening 18 of the mould opening 12. It is possible (although not illustrated) that a portion of the formulation 22 is received in the mold opening 12 through the second opening 18 due to capillary action.

Arrow 52 illustrates the supply of the mould elements and arrow 54 illustrates the ejection thereof, so that the method may preferably be implemented as a plow (plow) process and/or a roll (roll) process.

Fig. 1b illustrates a second state of the embodiment in fig. 1 a. Arrows 24 schematically illustrate the pressure exerted on the mould element 10 or the membrane 11. Preferably, the mould element has been compressed. As a result of the pressure applied, the mould element 10 is compressed such that the volume of the mould opening 12' has been reduced compared to the embodiment in fig. 1 a. Compression devices 37 (e.g., squeeze devices or roller devices) may be used to apply pressure on one or both sides of the die element 10.

Fig. 1b also illustrates a system 100 for producing microstructures having a mold element 10 and a compression device 37. The compression device 37 is in particular a squeezing device.

Fig. 1c illustrates another state according to the embodiment in fig. 1a and 1 b.

On the first side 16 of the mould element 10, an auxiliary element 26 is arranged, which is designed in particular as a film. Here, the auxiliary element 26 closes the first opening 14 of the reduced-volume mold opening 12'.

Fig. 1d illustrates a further state of the embodiment in fig. 1a to 1 c. In contrast to the embodiment in fig. 1b to 1c, the mould element 10 expands again, in particular relaxes (illustrated by arrow 28). It is particularly preferred that the mold element 10 elastically recovers itself by expansion. Thereby, the volume of the die opening 12 expands again. The volumetric expansion of the mold opening 12 causes a negative pressure in the mold opening 12. Since the first opening 14 of the mould opening 12 is closed, a suction effect is created at the second opening 18. As a result of the suction effect, the first agent 22 is sucked in, in particular into the mold opening 12, so that the mold opening 12 is now partially filled with the agent 22'. The entire mold opening 12 can also be filled with the first agent 22 by corresponding dimensions. It is possible that microstructures, in particular microneedles, are formed in the mold element 10 by curing of the formulation 22'.

The mould element 10 of fig. 2a corresponds substantially to the mould element 10 of fig. 1a to 1 b. Unlike the embodiment of fig. 1a to 1d, the tips of the mould openings 12 in fig. 2a are located in the protrusions 36 of the mould element 10. The second opening 18 of the mould element 12 of fig. 2a thus ends in this projection 36. The first formulation 22 is provided in a recess 32 of a formulation element 30 designed as a membrane 30. The recess 32 is located on a first side 34 of the formulation element 30, preferably the recess 32 generally corresponds to the negative of the protrusion 36.

Fig. 2a shows that the membrane 11 of the mould element 10 and the membrane 30 of the formulation element 30 are combined, in particular connected (combination illustrated from left to right).

Fig. 2b illustrates another state of the embodiment in fig. 2 a. Here, the mold element 10 and the formulation element 30 are combined such that the projections 36 are arranged in the recesses 32. A portion of the formulation 22 has entered the tip 42 of the die opening 12 through the second opening 18 due to capillary action.

Fig. 2c shows another state, preferably the embodiment of fig. 2b is supplied from the left side in the direction of arrow 52.

The compression means 37, which in this case comprise two offset rollers 38, 40, exert a pressure on the mould element 10 or compress the mould element (as illustrated by arrow 23'). As illustrated, the mold elements with the formulation elements 30 attached extend from left to right (in the direction of arrows 52, 54). The direction of rotation of the rollers 38, 40 is illustrated by arrow 56. As illustrated, it is preferred that roller 38 rotate clockwise and roller 40 rotate counterclockwise. The elastic mould element 10 is compressed due to the pressure exerted by the rollers 38, 40 on the mould element 10 (corresponding to arrow 23') and due to the longitudinal expansion caused in particular by the tension of the rollers 38, 40. As a result of this compression, the volume of the mold opening 12 of the mold element 10 is reduced. This change in volume of the die opening 12 is illustrated in region a. In this case, the mold element is already compressed in the region of the mold opening 12″ so that the volume of the mold opening 12' is reduced. However, in the region of the mold opening 12', the mold element 10 has not yet been compressed, so that the volume of the mold opening 12' is in an initial state.

As illustrated, the auxiliary element 26 is supplied in the direction of arrow 58 in the region between the rollers 38, 40. Here, the auxiliary element 26 covers the first side 16 of the compression mold element 10, so that the first opening 14 'of the reduced-volume mold opening 12' is closed.

After passing through the area between the rollers 38, 40, the mold elements relax, preferably elastically recover themselves. This is illustrated in region B. The volume of the mould opening 12 expands due to the elastic deformation of the mould element 10. This results in a negative pressure in the mould opening 12. Due to the negative pressure, the first agent 22 is sucked through the second opening 18 of the mould opening 12. The mold opening 12"", shown on the right, has been fully inflated such that a portion of the mold opening 12 ""' has been fully filled with the first formulation 22"". In contrast, the volume of the mold opening 12 '"has not yet fully expanded such that only a portion of the formulation 22" has been absorbed, while a portion of the formulation 22' remains in the recess 32. This retained formulation 22 'may also be absorbed as the mold opening 12' "continues to move and fully expands.

Fig. 2c also illustrates a subsystem 101 for producing microstructures having a compression device 37, a mould element 10, an auxiliary element 26 and a formulation element 30. The compression device 37 is in particular a squeezing device. Subsystem 101 corresponds to an embodiment of system 100 for producing microstructures according to the present invention.

Fig. 3 also shows the production state, preferably the embodiment in fig. 2b is supplied from the left in the direction of arrow 52. The embodiment in fig. 3 is in particular an alternative to the embodiment in fig. 2 c. The illustration in fig. 3 is similar to that in fig. 2 c.

The compression means 37, which in this case comprise two offset rolls 38, 40, bend the mould element 10 around the roll 40. As illustrated, the mold elements with the formulation elements 30 attached extend from left to right (in the direction of arrows 52, 54). The direction of rotation of the rollers 38, 40 is illustrated by arrow 56. As illustrated, it is preferred that roller 38 rotate clockwise and roller 40 rotate counterclockwise. By bending the mold element 10, there is a compression portion 72 (also referred to as a compression portion) and a tension portion 74 (also referred to as a tension portion) of the mold element 10 on either side of the neutral portion 70 (as exemplified by region B'). Compression (illustrated by arrow 76) results in a reduction of volume 13 'in the compressed portion of die opening 12'. However, in the stretched portion of the die opening 12", an increase in volume 13" is caused. Since the volume fraction of the compression portion is significantly larger than the portion located in the tension portion, a volume reduction of the die opening 12' is achieved as a whole.

However, in region a ', the mold element 10 is (yet) not bent, so that the volume of the mold opening 12' is (still) in the initial state.

After passing through the area between the rollers 38, 40, the mold element 10 returns to the unbent initial state. Thus, the total volume of the die opening increases, as opposed to the total volume in region B' decreasing. This results in a negative pressure in the mould opening 12. Due to the negative pressure, the first agent 22 is sucked through the second opening 18 of the mould opening 12.

Fig. 3 also illustrates a subsystem 101 for producing microstructures comprising the compression device 37, the mould element 10, the auxiliary element 26 and the formulation element 30. The compression means 37 are in particular bending means. Subsystem 101 corresponds to an embodiment of system 100 for producing microstructures according to the present invention.

Fig. 4 shows another state of the method for producing microstructures according to the present invention. The mould element 10 is supplied from the left side in the direction of arrow 52. The mold element 10 includes a plurality of mold openings 12. The underside of the mould element 10 is connected to the preparation element 30. Preferably, the mould element 10 is implemented according to the embodiment in fig. 1d or fig. 2c, wherein however the auxiliary element 26 is removed, in particular peeled off.

In the illustrated region C, the mold opening 12' has been partially filled with the first formulation 22', however, the region of the pyramid-shaped base of the mold opening 12' is empty. A preparation 50, preferably free of active ingredient, is applied on the first side 16 of the mould element 10 in the region of the first opening 14.

A second formulation element 116, which is specifically designed as a film, is supplied in the direction of arrow 60, which element covers the second formulation. Pressure is applied to the second formulation element 116 via the roller 110 such that the second formulation element 116 is connected to the mould element 10 by being pressed onto the mould element. Thus, the second formulation 50 is pressed into the empty portion of the mold opening 12'.

In the illustrated region D, the mold opening 12 "is thereby filled with the second formulation 50'. The mould opening 12 is thereby completely filled with a formulation which corresponds to the microstructure, in particular after curing.

Fig. 4 shows a subsystem 103 of the system 100 for producing microstructures.

Fig. 5 shows an embodiment of a system 100 for producing microstructures according to the present invention.

The system 100 is disposed in a housing 102. The housing is preferably sterile with respect to the environment. The supplied components are preferably sterilized and/or transferred through the mousehole into the housing 102 before being supplied. In particular, the housing 102 is an isolator. The film is preferably introduced into the system using a packaging tube.

The first formulation element 30 is supplied in the direction of arrow 52', in particular using a packaging tube 31. The auxiliary element 26, which is preferably designed as a film, is supplied in the direction of arrow 58. The auxiliary element 26 is supplied in particular in a packaging tube 47.

The area illustrated in block IIc is designed to correspond in particular to the embodiment in fig. 2c or fig. 3. The first formulation 22 is provided here by a first formulation dispenser 21 which applies the formulation 22 as droplets 22' onto the formulation element 30, in particular into recesses 32 of the formulation element 30.

After the zone IIc, the auxiliary element 26 is preferably discharged via a roller 108.

Subsequently, the first formulation 22 in the mold element 10' is preferably dried using the drying device 104 a.

Preferably, this is followed by a test of the mold element 10", in particular of the preferably cured formulation 22. The test is preferably performed by means of the test device 106 a. The test device is particularly configured as an optical device. It is particularly preferred that the test device comprises at least one camera.

The adjacent region III is preferably designed as illustrated in fig. 4. The second formulation 50 is provided in particular using a second formulation dispenser 51 which applies the formulation 50 as droplets 50 'onto the mould element 10' ". The second formulation element 60 is supplied in particular using a packaging tube 118. The second preparation element 60 comprises, in particular consists of, in particular a permeable and/or hygroscopic membrane.

Downstream of zone III, the mold element 10 is preferably ejected via roller 114. In this context, it is particularly preferred that the first formulation element 30 is discharged together therewith. However, it is also possible that the first formulation element 30 has been discharged at an earlier time (i.e. some time after the region IIc). Upon ejection of the mold element 10, the formulations 22, 50, which preferably combine to form the microstructures 120, are ejected. In this context, it is preferred that the microstructure 120 is for example adhesively connected to the second formulation element and that the demolding and further transport of the microstructure 120 is thereby performed.

The preferably connected formulations 22, 50 corresponding to the microstructure 120 to be produced are preferably dried before and/or during demolding. Drying may be performed using the drying device 104 b. However, in addition or as an alternative, air drying may also be performed using a membrane 60 that is preferably permeable and/or hygroscopic.

Preferably, the microstructures 120 are tested after deformation. Preferably, the testing is performed using the testing device 106 b. The test device comprises in particular at least one camera.

Subsequently, the microstructures 120 are preferably packaged. For this purpose, the blister film 122 is preferably supplied in the direction of arrow 62. This supply is performed in particular on the rollers 126, 128. The blister film 122 includes a plurality of blisters 123 open to the top.

In region E, the blister film 128 is bonded to the microstructures 120. In so doing, the microstructures 120 are received in the blister 123 such that the microstructures 124 of the blister package are obtained. These microstructures are ejected in the direction of arrow 54.

Claims

1. A method for producing a microstructure (120), in particular a microarray, comprising the steps of:

providing a planar mould element (10) comprising at least one mould opening (12) for a microstructure (120) to be produced, the at least one mould opening (12) having a first opening (14) and a second opening (18) located in particular opposite the first opening (14);

-providing a first formulation (22) at the second opening (18), the formulation preferably comprising an active ingredient;

generating a negative pressure in the mould opening (12); and

-absorbing the first agent (22) into the mould opening (12) through the second opening (18) due to the negative pressure in the mould opening (12).

2. The method according to claim 1, characterized by the steps of: expanding the volume of the mould opening (12) to generate the negative pressure in the mould opening (12).

3. The method according to claim 1 or 2, characterized by the further step, before the step of generating the negative pressure in the mould opening (12), in particular before the expansion of the volume of the mould opening (12): the volume of the mould opening (12) is reduced.

4. A method according to claim 3, characterized in that the mould element (10) is compressed, in particular pressed and/or bent, to reduce the volume of the mould opening (12).

5. Method according to claim 4, characterized in that the compression of the mould element (10) is performed using at least one roller (38; 40), preferably two rollers (38, 40), arranged on either side of the mould element (10).

6. The method according to any one of claims 1 to 5, characterized by the further step, preferably before the step of generating the negative pressure in the mould opening (12), particularly preferably before the expansion of the volume:

an auxiliary element (26), which in particular comprises an auxiliary film, is arranged on the side of the mould element (10) having the first opening.

7. The method according to any one of claims 1 to 6, characterized by the further step, preferably before the step of generating the negative pressure in the mould opening (12), particularly preferably before the compression of the mould element (10): the first opening of the mould opening (12) is preferably closed by means of the auxiliary element (26).

8. The method according to claim 6, characterized by the further step, after the first formulation (22) is absorbed into the first mould opening (12), of:

the auxiliary element (26) is preferably removed, in particular peeled, from the mould element (10).

9. The method according to any one of claims 1 to 8, characterized in that the at least one mould opening (12) is cylindrical or conical, preferably has a circular, triangular or quadrangular cross section, particularly preferably has a square cross section.

10. The method according to any one of claims 1 to 9, characterized in that the mould element (10) comprises, in particular consists of, a film.

11. The method according to any one of claims 1 to 10, characterized in that the mould element (10) is compressible, in particular elastically compressible.

12. The method according to any one of claims 1 to 11, characterized by the further step, after the uptake of the first formulation (22), of:

-providing a second preparation (50) at the first opening (14), the second preparation preferably being free of active ingredient; and

the second preparation (50) is absorbed into the mould opening (12) through the first opening (14), the second preparation (50) preferably being combined with the first preparation (22).

13. The method according to any one of claims 1 to 12, characterized in that providing the first formulation (22) is performed by using a first formulation element (30), preferably designed as a film, the first formulation element (30) comprising the first formulation (22); and/or

Providing the second formulation (50) is performed by using a second formulation element (116), preferably designed as a membrane, the second formulation element (116) comprising the second formulation (50).

14. The method according to any one of claims 1 to 13, characterized by the further step of: demolding the first formulation (22) and preferably the second formulation (50) which have been at least partially cured to form a microstructure (120) at the first opening of the mold opening (12).

15. The method of claim 14, wherein the step of providing the first information comprises,

the demolding is performed using a cover element, preferably comprising a cover film, which cover element is in particular combined with the formulation substance; and/or

The demolding is performed by removing, in particular peeling, the mold element (10).

16. The method according to any one of claims 1 to 15, characterized by the further step of: the demolded microstructure (120) is packaged with a blister element (122), which particularly preferably comprises a blister film.

17. The method according to any one of claims 1 to 16, characterized in that the method is performed using a system (100) according to claim 18 or 19.

18. A system (100) for producing microstructures (120), in particular for performing a method according to any one of claims 1 to 17, comprising:

a compressible mold element comprising at least one mold opening (12) for a microstructure (120) to be produced; and

compression means (37) preferably comprising at least one roller (38; 40),

the compression device is configured to compress the mold element (10).

19. The system according to claim 18, characterized in that the compression device (37) comprises two opposing rollers (38, 40), the rollers (38, 40) being arranged such that the mould element (10) can be compressed between the rollers (38, 40).